This project is designed to investigate the neural mechanisms of placebo analgesia. An innovative placebo protocol that assesses the placebo response to both visceral and cutaneous pain stimulation will be employed. Functional Magnetic Resonance Imaging (fMRI) will enable the characterization of brain mechanisms involved in placebo analgesia in a clinical population which experiences visceral pain as part of their clinical syndrome. This project will capitalize on previous work with Irritable Bowel Syndrome (IBS) patients where differential brain activation was demonstrated to visceral and cutaneous pain stimuli. In this same population a powerful and reliable placebo response to specific expectancy response sets has been demonstrated. The proposed project will combine these protocols to obtain brain images of IBS subject during natural history, placebo, and active agent (rectal lidocaine) conditions. It is anticipated that results will show that the placebo response will selectively activate specific brain regions. Neural activity (as measured by rCBF) will be greater in natural history conditions as compared to placebo conditions in the following brain regions: - lateral and/or medial thalamus, somatosensory areas 1 and 2, insular cortex, anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and prefrontal cortex. Furthermore, placebo mechanisms that operate primarily through attenuation of nociceptive signals at lower nervous system levels (spinal cord) will be evidenced by decreased thalamic, somatosensory, ACC, and PCC activation. Previous research indicates that expectancy and desire for pain relief will significantly predict the pain reduction from placebo. It is anticipated that these measures will also be associated with the above described brain activation patterns. By comparing the placebo conditions to the rectal lidocaine condition, brain and central nervous system related mechanisms versus peripheral (receptor site) related mechanisms will be differentiated. [unreadable] [unreadable]